PD-017 - A multicenter phase I/II study of TAS-102 with bevacizumab for metastatic colorectal cancer refractory to standard therapies (C-TASK FORCE)

Date 04 July 2015
Event WorldGI 2015
Session Posters
Topics Anti-Cancer Agents & Biologic Therapy
Colon Cancer
Rectal Cancer
Presenter T. Nishina
Citation Annals of Oncology (2015) 26 (suppl_4): 101-107. 10.1093/annonc/mdv234
Authors T. Nishina1, A. Ohtsu2, T. Matsumoto3, T. Kajiwara1, E. Shinozaki4, A. Sato1, K. Yamazaki1, T. Yoshino1, Y. Kuboki1, K. Shitara1, T. Tsushima1, W. Okamoto5, N. Mochizuki1, S. Nomura1
  • 1National Hospital Organization Shikoku Cancer Center, Matsuyama/JP
  • 2National Cancer Center, Kashiwashi/JP
  • 3Shikoku Cancer Center, Matsuyama/JP
  • 4Cancer Institute Hospital of JFCR, Koto-ku/JP
  • 5National Cancer Center Hospital East, Kashiwashi/JP

Abstract

Introduction

In global phase III RECOURSE trial, TAS-102 significantly improved overall survival (OS), progression-free survival (PFS) and disease control rate (DCR) over placebo for metastatic colorectal cancer (mCRC) patients (pts) refractory to standard therapies. In preclinical models, TAS-102 with bevacizumab (BEV) demonstrated enhanced activity against CRC cells compared with either drug alone. This phase I/II study was conducted to determine the recommended phase II dose (RP2D) and evaluate the efficacy, safety and pharmacokinetics of this combination in pts with mCRC refractory to standard therapies.

Methods

Eligibility criteria were: mCRC pts who were refractory or intolerant to fluoropyrimidines, irinotecan, oxaliplatin, anti-angiogenesis therapy and anti-EGFR antibody (if KRAS wild-type) and had no prior regorafenib treatment. Phase I was designed to determine RP2D in the dose de-escalation design of TAS-102 (35 mg/m2 BID on days 1–5 and 8–12 q4w for level 1 and 30 mg/m2 BID for level −1) with a fixed BEV dose (5 mg/kg q2w). Primary endpoint was centrally assessed PFS rate at 16 weeks in pts treated with RP2D. Using a single stage binomial design, this study required 21 pts, with a centrally assessed PFS rate at 16 weeks of 50% deemed promising and 25% unacceptable (alpha = 0.1; beta = 0.2).

Results

From February to July 2014, 25 pts were enrolled. In phase I, dose-limiting toxicity was not observed in 6 pts at level 1, which was determined as the RP2D. Centrally assessed PFS rate at 16 weeks (n = 21) was 42.9% (80% confidence interval: 27.8–59.0%). Median PFS and DCR by central assessment were 3.7 months and 64.0%, and by investigator assessment were 5.4 months and 72.0%, respectively (n = 25). Median OS was not reached. The most common grade 3 or worse adverse events were neutropenia (68%), febrile neutropenia (8%), thrombocytopenia (4%) and anorexia (4%) without unexpected safety signals. Drug–drug interaction was not indicated by pharmacokinetic analysis.

Conclusion

The combination of TAS-102 with BEV showed promising antitumor activity with acceptable toxicity for mCRC pts; biomarker analysis will be presented. Clinical trial information: UMIN000012883.